Thiazolidine derivatives

ABSTRACT

Compounds of the formula:   WHEREIN R represents alkyl, R1 represents hydrogen, alkyl or phenyl, and R2 represents alkyl, alkyl substituted by halogen, phenyl or phenyl carrying one, two or three substituents selected from halogen and alkyl, alkoxy and alkanoylamino radicals, or a naphthyl radical, are useful as fungicides.

D United States Patent 1 [111 3,868,382 Giraudon Feb. 25, 1975 THIAZOLIDINE DERIVATIVES Primary ExaminerRichard J. Gallagher [75] Inventor. Raymond Giraudon Attorney, Agent, or FirmStevens, Davis, Miller &

Lesigny, Seine-et-Marne, France $3 1 ABSTRACT [73] Assignee: Rhone-Poulenc S.A., Paris, France Compounds of the formula: I22 I-ik-d: Ill-c. 2), I972 III I Appl. No.13l9,877

N [30] Foreign Application Priority Data Jan. I2. 1972 France 72.00947 ILCOOR SO [52] US. Cl. 260/306.7 T, 260/470, 260/556 A, NH- 2 R2 260 556 B, 424 270 [5]] Int Cl I I I i Co-Id 9/1/16 wherein R represents alkyl, R represents hydrogen, [58] Field D H 260/306 7 alkyl or phenyl, and R represents alkyl, alkyl substituted by halogen, phenyl or phenyl carrying one, two [56] References Cited or three substituents selected from halogen and alkyl,

alkoxy and alkanoylamino radicals, or a naphthyl radi- UNITED STATES PATENTS cal, are useful as fungicides. 3,759,938 9/1973 Giraudon 260/306.7

14 Claims, N0 Drawings THIAZOLIDINE DERIVATIVES This invention relates to new thiazolidine derivatives, to a process for their preparation and to compositions containing them.

The thiazolidine derivatives of the present invention are those of the general formula:

TV- R1 N s -coon NHSO2-R2 wherein R represents a lower alkyl radical, R, represents a hydrogen atom, a lower alkyl radical or a phenyl radical, and R represents a lower alkyl radical optionally substituted by one or more halogen atoms, a phenyl radical optionally carrying one, two or three substituents selected from halogen atoms and lower alkyl, lower alkoxy and lower alkanoylamino radicals, or a naphthyl radical. When the symbol R represents a phenyl radical carrying two or three substituents, the substituents may be the same or different.

The qualification lower" as applied in this specifica tion to alkyl. alkoxy and alkanoylamin'o radicals means that the radical contains at most four carbon atoms.

According to a feature of the invention, the thiazolidine derivatives of general formula I are prepared by reacting a thiourea of the general formula:

NH- CS-NH-COOR (wherein R and R are as hereinbefore defined) with an acid halide of the general formula:

III

(wherein R is as hereinbefore defined),optionally prepared in situ, with an aniline derivative of the general formula:

wer

wherein R is as hereinbefore defined. The reaction is generally carried out in an organic solvent, e.g., acetone, and at a temperature between 0C. and the boiling point of the reaction mixture.

The aniline derivatives of general formula V can be obtained by reaction of a sulphonyl chloride of the general formula:

(wherein R is as hereinbefore defined) with a phenylenediamine according to the method of E. Riesz et coll., Monatsh., 58, 147 (1931), or with a nitroaniline followed by reduction of the nitro group in the product obtained by means of a suitable reducing agent according to the method of Lellmann, Ann., 221, 17 (1883) or that of Morgan and Mickelthwait, J. Chem. Soc., 87, (1905).

The thiazolidine derivatives of general formula I possess useful fungicidal properties; they have particularly interesting contact activity against cucumber mildew (Erysiphe cichoracearum), apple mildew (Podosphaera leucotricha), bean anthracnose (Collerotrichum lindemuthianum) and wheat rust (Puccinia glumarum) when applied at quantities of between 10 and 50 g. per heetolitre of liquid diluent. They furthermore have the advantage of being systemic, in particular when they are applied by sprinkling the soil with liquid compositions containing them, against bean anthracnose and against cucumber mildew at doses greater than or equal to 0.1 g./hectolitre.

Preferred thiazolidine derivatives of general formula I are those wherein R represents a methyl or ethyl radical and R, represents a hydrogen atom, and especially those wherein the substituent NHSO -R (wherein R is as hereinbefore defined) is in the 2- position of the phenyl ring, and more particularly those such compounds wherein R represents a methyl radical. Of particular importance are 2- methoxycarbonylimino-3-(2-methylsulphonylaminophenyl)-thiazolidin-4-one, Z-methoxyearbonylimino-3 (2-phenylsulphonylamino-phenyl)-thiazolidin-4-one and Z-methoxycarbonylimino-3-(2-4- methylphenylsulphonylamino-phenyl)-thiazolidin- 4-one.

The following Examples illustrate the preparation of thiazolidine derivatives of general formula I by the process of the invention.

EXAMPLE 1 Chloroacetyl chloride (13.6 g. is added, over the course of 4 minutes and with stirring, to a solution of l-methoxycarbonyl-3-(2-methylsulphonylaminophenyl)-thiourea (28 g.) and N,N-dimethylaniline (26.6 g.) in N-methylpyrrolid-2-one (90 cc.). The temperature of the reaction mixture rises from 23 to 63C. during the addition. The reaction mixture is kept at 45C. for 5 hours and is then poured into water (1,000 cc.). The mixture is extracted with methylene chloride (1,000 cc. followed by 500 cc.). After treating the methylene chloride extracts with decolourizing charcoal, drying over anhydrous sodium sulphate and evaporating the solvent under reduced pressure, an oily residue (40 g.) is obtained which is taken up in ethanol (500 cc.). The crystalline product obtained melts at about 210C After purification by washing with acetonitrile, 2-methoxycarbonylimino-3-(2- methylsulphonylamino-phenyl)-thiazolidin4-one (9.4 g.), m.p. 228C, is obtained.

EXAMPLE 2 Chloroacetyl chloride (9.2 g.) is added, over the course of 20 minutes and with stirring, to a solution of l-mcthoxycarbonyl-3-(2-phenylsulphonylaminophenyl)-thiourea (24.5 g.) in N-methylpyrrolid-Z-one (55 cc.). The temperature is up to 40C. at the end of the addition. Stirring is continued for 3 hours at a temperature of about 20C. and then the reaction mixture is diluted with ethanol (150 cc.). The crystalline precipitate obtained is filtered off and washed with ethanol (100 cc.). After drying, 2-methoxycarbonylimino-3-(2- phenylsulphonylamino-phcnyl)-thiazolidin-4-one (8 g), m.p. 244C, is obtained.

The following products of general formula I are prepared following the procedure of Example l or 2 using appropriate starting materials of general formula II.

2-methoxycarbonylimino-3-(2- isopropylsulphonylaminophenyl)-thiazolidin-4-one, m.p. 205C;

2-methoxycarbonylimino-3-(2- iodomethylsulphonylaminophenyl)-thiazolidin- 4-one, m.p. 220C;

2-methoxycarbonylimino-3-(2-butylsulphonylaminophenyl)-thiazolidin-4-one, m.p. 208C;

2-methoxycarbonylimino-3-(2-2'- naphthylsulphonylaminophenyl)-thiazolidin-4-one,

m.p. 246C;

Z-methoxycarbonylimino-3-(2-4- acetamidophenylsulphonylamino-phenyl)- thiazolidin-4-one, m.p. 190C;

Z-mcthoxycarbonylimin-3-(2-4'- methylphenylsulphonylaminophenyl)-thiazolidin- 4-one. m.p. 275C., and

2-methoxycarbonylimino-3-(2-2, dichlorophenylsulphonylamino-phenyl)-thiazolidin- 4-one, m.p. 275C.

The starting materials of the general formula ll can be prepared by using the method described below for the preparation of l-methoxycarbonyl-3-(Z-phenylsulphonylamino-phenyl)-thiourea.

Methyl chlororformate (22.2 g.) is added, with stirring, to a solution of potassium thiocyanate (24.4 g.) in acetone (200 cc.). The temperature of the reaction mixture rises gradually to 35C. The mixture is then heated at the reflux temperature for 30 minutes. After cooling, Z-phenylsulphonylamino-aniline (24.8 g.) is added over the course of a few minutes and without allowing the temperature to exceed 20C. The reaction is very slightly exothermic. The reaction mixture is stirred for 16 hours at'a temperature of about 20C. Water (200 cc.) is then added and the mixture is stirred for 1 hour at a temperatue of about 20C. The crystalline precipitate which has appeared is filtered off and washed with water (2 X 50 cc.) followed by ethanol (2 X 50 cc.). After drying, l-methoxycarbonyl-3-(2- phenylsulphonylamino-phenyl)-thiourea (35 g.), m.p. 224C, is obtained.

By carrying out the same procedure, the following thioureas of general formula ll are obtained:

l-methoxycarbonyl-3-( 2-methylsulphonylaminophenyl)-thiourea, m.p. 194C; l-methoxycarbonyl-3-( 2-isopropylsulphonylaminophenyl)-thiourea, m.p. 204C; l-methoxycarbonyl-3-(2-iodomethylsulphonylaminophenyl)-thiourea, m.p. 126C; 1-methoxycarbonyl-3-(2-butylsulphonylaminophenyl)-thiourea, m.p. 150C; l-methoxycarbonyl-3-(2-2-naphthylsulphonylaminophenyl)-thiourea, m.p. 234C; 1-methoxycarbonyl-3-(2-4-acetamidophenylsulphonylaminophenyl)-thiourea, m.p. 220C; l-methoxycarbonyl-3-(2-4- methylphenylsulphonylaminophenyl)-thiourea, m.p. 226C; and l-methoxycarbonyl-3-(2-2', 5-dichlorophenylsulphonylamino-phenyl)-thiourea, m.p. 214C.

According to a further feature of the present invention, there are'provided fungicidal compositions which contain, as the active ingredients, at least one thiazolidine derivative of general formula I in association with one or more diluents or adjuvants compatible with the thiazolidine derivative(s) and suitable for use in agricultural fungicidal compositions. These compositions can optionally contain other compatible pesticides, such as insecticides or fungicides (e.g., maneb). Preferably the compositions contain between 0.005 and percent by weight of thiazolidine derivative.

The compositions may be solid if there is employed a powdered solid compatible diluent such as talc, calcined magnesia, kie'selguhr, tricalcium phosphate, powdered cork, adsorbent charcoal, or a clay such as kaolin or bentonite. These solid compositions are preferably prepared by grinding the thiazolidine derivative with the solid diluent, or by impregnating the solid diluent with a solution of the thiazolidine derivative in a volatile solvent, evaporating the solvent, and if necessary grinding the product so as to obtain a powder.

Instead of a solid diluent, there may be used a liquid in which the thiazolidine derivative is dissolved or dispersed. The compositions may thus take the form of suspensions, emulsions or solutions in organic or aqueous-organic media, for example aromatic hydrocarbons such as toluene or xylene, mineral, animal or vegetable oils, or acetophenone, or mixtures of these diluents. The compositions in the form of suspensions, emulsions or solutions may contain wetting, dispersing or emulsifying agents of the ionic or non-ionic type, for example sulphoricinoleates, quaternary ammonium derivatives or products based on condensates of ethylene oxide such as the condensates of ethylene oxide with octylphenol, or fatty acid esters of anhydrosorbitols which have been rendered soluble by etherification of the free hydroxyl groups by condensation with ethylene oxide. It is preferable to use agents of the non-ionic type because they are not sensitive to electrolytes. When emulsions are required the thiazolidine derivatives may be EXAMPLE 3 A wettable powder containing 50 percent by weight of active material and having the following composition is prepared in accordance with the usual technique:

Z-methoxycarbonylimino-3-(Z-methylsulphonylaminophenyl)-thiazolidin-4 one kieselguhr polyoxyethylene-sorbitan monooleate (non-ionic emulsifier) calcium lignosulphonate I claim: l. 'l'hiamlidinc derivatives of the formula:

wherein R represents alkyl of l to 4 carbon atoms, R represents hydrogen, alkyl of l to 4 carbon atoms or phenyl. and R represents alkyl of l to 4 carbon atoms, alkyl of l to 4 carbon atoms substituted by halogen, phenyl or phenyl carrying one, two or three substitucnts selected from the class consisting of halogen and alkyl. alkoxy and alkanoylamino radicals, or a naphthyl radical. the said alkyl, alkoxy and alkanoylamino radicals having 1 through 4 carbon atoms.

2. Thiazolidine derivatives according to claim 1 wherein R represents methyl or ethyl and R represents hydrogen.

3. Thiazolidine derivatives according to claim 1 in which the substituent NHSO R R being as defined in claim 1, is in the 2-position of the phenyl ring.

4. Thiazolidine derivatives according to claim 1 wherein R represents methyl or ethyl, R represents hydrogen and the substituent NH-SO R R being as defined in claim 1, is in the 2-position of the phenyl ring.

5. Thiazolidine derivatives according to claim 4 wherein R represents methyl.

6. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2- methylsulphonylaminophenyl)-thiazolidin-4-one.

7. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2- phenylsulphonylamino-phenyl)-thiazolidin-4-one.

8. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonyliminc-3-(2- isopropylsulphonylamino-phenyl)-thiazolidin-4-one.

9. The thiazolidine derivative according to claim 1 which is 2-meth0Xycarbonylimino-3-(2- iodomethylsulphonylaminophenyl)-thiazolidin-4-one.

10. The thiazolidine derivative according to claim 1 which is Z-methoxycarbonylimino-3-(2- butylsulphonylaminophenyl)-thiazolidin-4-onc.

11. The thiazolidine derivative according to claim 1 which is Z-methoxycarbonylimino-3-(2-2- naphthylsulphonylamino-phenyl)-thiazolidin-4-one.

12. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-4- acetamidophenylsulphonylamino-phenyl)-thiazolidin- 4-one.

13. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-4- methylphenylsulphonylamino-phenyl)-thiazolidin- 4-one.

14. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-2', 5- dichlorophenylsulphonylamino-phenyl)-thiazolidin- 

1. THIAZOLIDINE DERIVATIVES OF THE FORMULA:
 2. Thiazolidine derivatives according to claim 1 wherein R represents methyl or ethyl and R1 represents hydrogen.
 3. Thiazolidine derivatives according to claim 1 in which the substituent -NH-SO2-R2, R2 being as defined in claim 1, is in the 2-position of the phenyl ring.
 4. Thiazolidine derivatives according to claim 1 wherein R represents methyl or ethyl, R1 represents hydrogen and the substituent -NH-SO2-R2, R2 being as defined in claim 1, is in the 2-position of the phenyl ring.
 5. Thiazolidine derivatives according to claim 4 wherein R represents methyl.
 6. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-methylsulphonylaminophenyl)-thiazolidin-4-one.
 7. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-phenylsulphonylamino-phenyl)-thiazolidin-4-one.
 8. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-isopropylsulphonylamino-phenyl)-thiazolidin-4 -one.
 9. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-iodomethylsulphonylamino-phenyl)-thiazolidin-4 -one.
 10. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-butylsulphonylamino-phenyl)-thiazolidin-4-one.
 11. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-2''-naphthylsulphonylamino-phenyl)-thiazolidin-4 -one.
 12. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-4''-acetamidophenylsulphonylamino-phenyl) -thiazolidin-4-one.
 13. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-4''-methylphenylsulphonylamino-phenyl) -thiazolidin-4-one.
 14. The thiazolidine derivative according to claim 1 which is 2-methoxycarbonylimino-3-(2-2'', 5''-dichlorophenylsulphonylamino-phenyl)-thiazolidin-4-one. 